Carcinoma of the esophagus and carcinoma of the pancreas are among the most lethal of human neoplasms. Efforts to devise successful therapeutic regimens for the primary neoplasm are hampered by lack of an animal model suitable for the study of surgical procedures or radiation therapies appropriate for use in man. Using carcinogens with proven effect in small animals, we have successfully induced invasive bronchogenic carcinoma in dogs. In this application, we propose to extend this approach to the development of carcinoma of the esophagus and carcinoma of the pancreas in dogs. Achievement of a predictable model of esophageal and pancreatic cancer, in which the lesion is reproducible at pre-selected localized sites, will provide 1) opportunities for studying the transition of normal tissues into pre-neoplastic and neoplastic lesions, 2) a preparation for serial diagnostic studies utilizing methods feasible in man but not possible in the small animals usually employed in carcinogenesis research, and 3) a potential for meaningful therapeutic investigations using this large animal model for esophageal and pancreatic carcinoma. As the work progresses and neoplastic lesions are produced, collaborative projects conducted in cooperation with other members of the City of Hope Cancer Research Center will be developed. These will include basic immunologic and cytogenetic studies of the evolving tumors, and multimodality therapeutic approaches involving radiation and medical oncology.